The effects of the EW dipeptide optical and chemical isomers on the CFU-S population in intact and irradiated mice

Abstract

The influence of Glu–Trp (EW) synthetic dipeptide isomers on hemopoietic progenitor cells and certain immune response reactions is determined by their optical and chemical properties. Thus, the all l-amino acid containing dipeptides l-Glu–l-Trp and l-γGlu–l-Trp have no effect on proliferation of committed and pluripotent CFU-S in intact bone marrow. The optical isomers of the Glu residue are an essential determinant of the EW dipeptide biological activity. The inversion of the amino acid optical form imparts suppressor properties: d-Glu–d-Trp, d-γGlu–d-Trp, d-Glu–l-Trp and d-γGlu–l-Trp inhibit proliferation of hemopoietic progenitors in intact bone marrow. The type of the peptide bond between l-Glu and Trp is another important factor for the biological activity of the l-Glu-containing peptides. Unlike l-Glu–d-Trp with α-peptide bond, the dipeptide l-γGlu–d-Trp with γ-peptide bond stimulates CFU-S-8 proliferation in intact bone marrow. The diverse effects of the EW optical isomers on hemopoietic progenitors underlie the radioprotective properties of the d-Glu-containing dipeptides and the radiotherapeutic ones of the l-Glu dipeptides. In animals, pre-irradiation injection of d-Glu–d-Trp, d-γGlu–d-Trp, d-Glu–l-Trp, d-γGlu–l-Trp, or post-irradiation injection of l-Glu–l-Trp, l-γGlu–l-Trp promoted regeneration of the hemopoietic progenitor population.